The invention relates generally to compositions, methods and kits for assaying effect of materials on complement activation.
Materials such as surgical instruments or laboratory containers that contact blood or blood fractions sometimes activate the complement cascade. Activation of the complement system can occur via two distinct routes—the classical and the alternative pathway. In the course of complement activation, biologically active factors are released. These factors enhance the immune response by directing neutrophil migration, promoting immune adherence, increasing vascular permeability, and interacting with other inflammatory systems.
Initiation of the classical pathway begins when antibody binds antigen. The classical pathway components are designated C1 (with active products C1q, C1r, and C1s), C4 (active products C4a, C4b), C2 (active products C2a, C2b), C3, C5, C6, C7, C8, and C9. The alternative pathway provides natural, non-immune defense against microbial infections. In addition, this pathway amplifies antibody-antigen reactions. Alternative pathway recognition occurs in the presence of C3b and an activating substance such as bacterial lipoprotein, surfaces of certain parasites, yeasts, viruses and other foreign body surfaces. The alternative pathway components are designated Factor B, Factor D, and Properdin. Both pathways involve C3 participation, hence measurement of C3 activity can be used as an indicator of complement activation via either pathway.
Because complement activation up-regulates immune responses such as cell lysis, inflammation, and secretion of immunoregulatory molecules, testing of complement activation by materials used for the construction of medical devices may avoid these undesired results by allowing the user to select materials with low complement activation.
Thus, there is a need to develop newer techniques for assaying complement activation accurately to assess materials that come in contact with blood or blood components.